title: Beta-amyloid oligomerisation monitored by intrinsic tyrosine fluorescence.
abstract: Aggregation of the peptide beta-amyloid is known to be associated with Alzheimer's disease. According to recent findings the most neurotoxic aggregates are the oligomers formed in the initial stages of the aggregation process. Here we use beta-amyloid's (Aβ's) intrinsic fluorophore tyrosine to probe the earliest peptide-to-peptide stages of aggregation, a region often merely labelled as a time lag, because negligible changes are observed by the commonly used probe ThT. Using spectrally resolved fluorescence decay time techniques and analysis we demonstrate how the distribution of 3 rotamer conformations of the single tyrosine in Aβ tracks the aggregation across the time lag and beyond according to the initial peptide concentration. At low Aβ concentrations (≤5 μM), negligible aggregation is observed and this is mirrored by little change in the fluorescence decay parameters, providing a useful baseline for comparison. At higher concentrations (≈50 μM), and contrary to what is generally accepted from ThT studies the rate of aggregation can be described by an exponential growth to a plateau in terms of the relative contributions of two of the three rotamers, with a characteristic aggregation time of ≈33 h.
authors.affiliation: Photophysics group, Centre for Molecular Nanometrology, Department of Physics, Scottish Universities Physics Alliance, University of Strathclyde, 107 Rottenrow, Glasgow G4 0NG, UK.
authors.forename: Mariana
authors.initials: M
authors.lastname: Amaro
authors.forename: David J S
authors.initials: DJ
authors.lastname: Birch
authors.forename: Olaf J
authors.initials: OJ
authors.lastname: Rolinski
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence / Q000379:methods*; D014443:Tyrosine
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D014443:Tyrosine